Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population.

Background: Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to better understand disease mechanisms. Here, we performed eQTL mapping in subcutaneous (S) and visceral (V) adipose tissue from 106 Greek individuals (Greek Metabolic study, GM) and compared our findings to those from the Genotype-Tissue Expression (GTEx) resource.

Bee foraging preferences, microbiota and pathogens revealed by direct shotgun metagenomics of honey.

Honeybees (Apis mellifera) continue to succumb to human and environmental pressures despite their crucial role in providing essential ecosystem services. Owing to their foraging and honey production activities, honeybees form complex relationships with species across all domains, such as plants, viruses, bacteria and other hive pests, making honey a valuable biomonitoring tool for assessing their ecological niche. Thus, the application of honey shotgun metagenomics (SM) has paved the way for a detailed description of the species honeybees interact with.

Hnf1b haploinsufficiency differentially affects developmental target genes in a new renal cysts and diabetes mouse model.

Heterozygous mutations in HNF1B cause the complex syndrome renal cysts and diabetes (RCAD), characterized by developmental abnormalities of the kidneys, genital tracts and pancreas, and a variety of renal, pancreas and liver dysfunctions. The pathogenesis underlying this syndrome remains unclear as mice with heterozygous null mutations have no phenotype, while constitutive/conditional Hnf1b ablation leads to more severe phenotypes. We generated a novel mouse model carrying an identified human mutation at the intron-2 splice donor site.

Decoding the Reproductive System of the Olive Fruit Fly, .

In most diploid organisms, mating is a prerequisite for reproduction and, thus, critical to the maintenance of their population and the perpetuation of the species. Besides the importance of understanding the fundamentals of reproduction, targeting the reproductive success of a pest insect is also a promising method for its control, as a possible manipulation of the reproductive system could affect its destructive activity. Here, we used an integrated approach for the elucidation of the reproductive system and mating procedures of the olive fruit fly, .

Bacterial production and direct functional screening of expanded molecular libraries for discovering inhibitors of protein aggregation.

Protein misfolding and aggregation are associated with a many human disorders, including Alzheimer's and Parkinson's diseases. Toward increasing the effectiveness of early-stage drug discovery for these conditions, we report a bacterial platform that enables the biosynthesis of molecular libraries with expanded diversities and their direct functional screening for discovering protein aggregation inhibitors. We illustrate this approach by performing, what is to our knowledge, the largest functional screen of small-size molecular entities described to date.

Divergent Innate and Epithelial Functions of the RNA-Binding Protein HuR in Intestinal Inflammation.

HuR is an abundant RNA-binding protein acting as a post-transcriptional regulator of many RNAs including mRNAs encoding inflammatory mediators, cytokines, death signalers and cell cycle regulators. In the context of intestinal pathologies, elevated HuR is considered to enhance the stability and the translation of pro-tumorigenic mRNAs providing the rationale for its pharmacological targeting. However, HuR also possesses specific regulatory functions for innate immunity and cytokine mRNA control which can oppose intestinal inflammation and tumor promotion.

The future of metabolomics in ELIXIR.

Metabolomics, the youngest of the major omics technologies, is supported by an active community of researchers and infrastructure developers across Europe. To coordinate and focus efforts around infrastructure building for metabolomics within Europe, a workshop on the "Future of metabolomics in ELIXIR" was organised at Frankfurt Airport in Germany. This one-day strategic workshop involved representatives of ELIXIR Nodes, members of the PhenoMeNal consortium developing an e-infrastructure that supports workflow-based metabolomics analysis pipelines, and experts from the international metabolomics community.

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature.

Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression.

The whole genome sequence of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), reveals insights into the biology and adaptive evolution of a highly invasive pest species.

Background: The Mediterranean fruit fly (medfly), Ceratitis capitata, is a major destructive insect pest due to its broad host range, which includes hundreds of fruits and vegetables. It exhibits a unique ability to invade and adapt to ecological niches throughout tropical and subtropical regions of the world, though medfly infestations have been prevented and controlled by the sterile insect technique (SIT) as part of integrated pest management programs (IPMs). The genetic analysis and manipulation of medfly has been subject to intensive study in an effort to improve SIT efficacy and other aspects of IPM control.

A Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fate.

The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation, and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. We identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells.

Next-Generation Sequencing Analysis Reveals Differential Expression Profiles of MiRNA-mRNA Target Pairs in KSHV-Infected Cells.

Kaposi's sarcoma associated herpesvirus (KSHV) causes several tumors, including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). Cellular and viral microRNAs (miRNAs) have been shown to play important roles in regulating gene expression. A better knowledge of the miRNA-mediated pathways affected by KSHV infection is therefore important for understanding viral infection and tumor pathogenesis.

The molecular biology of the olive fly comes of age.

Background: Olive cultivation blends with the history of the Mediterranean countries since ancient times. Even today, activities around the olive tree constitute major engagements of several people in the countryside of both sides of the Mediterranean basin. The olive fly is, beyond doubt, the most destructive pest of cultivated olives.

Olive fly transcriptomics analysis implicates energy metabolism genes in spinosad resistance.

Background: The olive fly, Bactrocera oleae, is the most devastating pest of cultivated olives. Its control has been traditionally based on insecticides, mainly organophosphates and pyrethroids. In recent years, the naturalyte spinosad is used against the olive fly.

Integrated analysis of microRNA and mRNA expression and association with HIF binding reveals the complexity of microRNA expression regulation under hypoxia.

Background: In mammalians, HIF is a master regulator of hypoxia gene expression through direct binding to DNA, while its role in microRNA expression regulation, critical in the hypoxia response, is not elucidated genome wide. Our aim is to investigate in depth the regulation of microRNA expression by hypoxia in the breast cancer cell line MCF-7, establish the relationship between microRNA expression and HIF binding sites, pri-miRNA transcription and microRNA processing gene expression.

Methods: MCF-7 cells were incubated at 1% Oxygen for 16, 32 and 48 h.

DIANA-microT web server v5.0: service integration into miRNA functional analysis workflows.

MicroRNAs (miRNAs) are small endogenous RNA molecules that regulate gene expression through mRNA degradation and/or translation repression, affecting many biological processes. DIANA-microT web server (http://www.microrna.

DIANA-LncBase: experimentally verified and computationally predicted microRNA targets on long non-coding RNAs.

Recently, the attention of the research community has been focused on long non-coding RNAs (lncRNAs) and their physiological/pathological implications. As the number of experiments increase in a rapid rate and transcriptional units are better annotated, databases indexing lncRNA properties and function gradually become essential tools to this process. Aim of DIANA-LncBase (www.

Use of mutagenesis, genetic mapping and next generation transcriptomics to investigate insecticide resistance mechanisms.

Insecticide resistance is a worldwide problem with major impact on agriculture and human health. Understanding the underlying molecular mechanisms is crucial for the management of the phenomenon; however, this information often comes late with respect to the implementation of efficient counter-measures, particularly in the case of metabolism-based resistance mechanisms. We employed a genome-wide insertional mutagenesis screen to Drosophila melanogaster, using a Minos-based construct, and retrieved a line (MiT[w(-)]3R2) resistant to the neonicotinoid insecticide Imidacloprid.

DIANA miRPath v.2.0: investigating the combinatorial effect of microRNAs in pathways.

MicroRNAs (miRNAs) are key regulators of diverse biological processes and their functional analysis has been deemed central in many research pipelines. The new version of DIANA-miRPath web server was redesigned from the ground-up. The user of DNA Intelligent Analysis (DIANA) DIANA-miRPath v2.

Identification of microRNA-221/222 and microRNA-323-3p association with rheumatoid arthritis via predictions using the human tumour necrosis factor transgenic mouse model.

Objective: To identify novel microRNA (miR) associations in synovial fibroblasts (SF), by performing miR expression profiling on cells isolated from the human tumour necrosis factor (TNF) transgenic mouse model (TghuTNF, Tg197) and patients biopsies.

Methods: miR expression in SF from TghuTNF and wild-type (WT) control mice were determined by miR deep sequencing (miR-seq) and the arthritic profile was established by pairwise comparisons. Quantitative PCR analysis was utilised for profile validation, miR and gene quantitation in patient SF.

Accurate microRNA Target Prediction Using Detailed Binding Site Accessibility and Machine Learning on Proteomics Data.

MicroRNAs (miRNAs) are a class of small regulatory genes regulating gene expression by targeting messenger RNA. Though computational methods for miRNA target prediction are the prevailing means to analyze their function, they still miss a large fraction of the targeted genes and additionally predict a large number of false positives. Here we introduce a novel algorithm called DIANA-microT-ANN which combines multiple novel target site features through an artificial neural network (ANN) and is trained using recently published high-throughput data measuring the change of protein levels after miRNA overexpression, providing positive and negative targeting examples.

Functional microRNA targets in protein coding sequences.

Motivation: Experimental evidence has accumulated showing that microRNA (miRNA) binding sites within protein coding sequences (CDSs) are functional in controlling gene expression.

Results: Here we report a computational analysis of such miRNA target sites, based on features extracted from existing mammalian high-throughput immunoprecipitation and sequencing data. The analysis is performed independently for the CDS and the 3(')-untranslated regions (3(')-UTRs) and reveals different sets of features and models for the two regions.

TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support.

As the relevant literature and the number of experiments increase at a super linear rate, databases that curate and collect experimentally verified microRNA (miRNA) targets have gradually emerged. These databases attempt to provide efficient access to this wealth of experimental data, which is scattered in thousands of manuscripts. Aim of TarBase 6.

A computational exploration of bacterial metabolic diversity identifying metabolic interactions and growth-efficient strain communities.

Background: Metabolic interactions involve the exchange of metabolic products among microbial species. Most microbes live in communities and usually rely on metabolic interactions to increase their supply for nutrients and better exploit a given environment. Constraint-based models have successfully analyzed cellular metabolism and described genotype-phenotype relations.

DIANA-microT Web server upgrade supports Fly and Worm miRNA target prediction and bibliographic miRNA to disease association.

microRNAs (miRNAs) are small endogenous RNA molecules that are implicated in many biological processes through post-transcriptional regulation of gene expression. The DIANA-microT Web server provides a user-friendly interface for comprehensive computational analysis of miRNA targets in human and mouse. The server has now been extended to support predictions for two widely studied species: Drosophila melanogaster and Caenorhabditis elegans.